Despite advances in both clinical and basic research dedicated to reducing mortality rates and improving survival, cancer remains the leading cause of death among patients under 85 years of age in the United States. Most deaths from cancer do not result from the primary tumor but rather from the later metastasis. As a result, systemic therapy has become an essential component of metastatic cancer management. Systemic therapy has been limited to chemotherapy and biologic response modifiers. While new therapeutic agents like docetaxel, pernetrexed and erlotinib have been demonstrated as being effective in treating patients with advanced lung cancer, clinical responses to treatment and improved survival have been modest. The limited success of systemic chemotherapy thus underscores the need in developing adjunctive therapies.
Cancer vaccine therapy appears to be an attractive approach for cancer treatment because of its potential in eradicating systemic tumors at multiple sites and specificity in discriminating normal cells from neoplastic cells. Unlike most vaccines for infectious agents, the goal of cancer vaccination is therapeutic and this can be achieved by activating immune responses against tumor antigens. The immune response can be crudely divided into either antibody responses or T-cell responses. Antibodies recognize and bind to conformational determinants on cell surface proteins, and can kill the cell by either antibody-dependent cellular cytotoxicity or complement-mediated cell lysis. Conversely, T cells recognize small peptides presented on the cell surface on major histocompatibility (MHC) antigens, and T-cell activation requires a co-stimulatory signal which is usually present on the cell surface of antigen-presenting cells. However, attempts to exploit the immune system as a therapeutic strategy in cancer treatment have to overcome the host's inability to develop effective endogenous immunity against cancer.
The notion of directing the immune response towards a selected antigen should give potentially greater control of the immune response. However tumor-associated antigens have not been identified for most tumors, and where these have been identified, they may not be the most potent antigens involved in the rejection of that particular tumor, so that vaccine design may be suboptimal.
Therefore, a heretofore unaddressed need exists in the art to address the aforementioned deficiencies and inadequacies, especially in connection with antigen-specific cancer vaccines.